DNA binding affinity of bisguanidine and bis(2-aminoimidazoline) derivatives with in vivo antitrypanosomal activity

J Med Chem. 2006 Jun 15;49(12):3748-52. doi: 10.1021/jm060295c.

Abstract

A new antitrypanosomal hit compound that cures an acute (STIB 900) mouse model of Trypanosoma brucei rhodesiense trypanosomiasis is described. This bis(2-aminoimidazolinium) dicationic compound proved to be an excellent DNA minor groove binder, suggesting a possible mechanism for its trypanocidal activity. From these studies, the 4,4'-diaminodiphenylamine skeleton emerged as a good scaffold for antitrypanosomal drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA / chemistry*
  • Female
  • Guanidines / chemical synthesis*
  • Guanidines / chemistry
  • Guanidines / pharmacology
  • Imidazolines / chemical synthesis*
  • Imidazolines / chemistry
  • Imidazolines / pharmacology
  • Mice
  • Nucleoside Transport Proteins / genetics
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanosoma brucei brucei / genetics
  • Trypanosoma brucei brucei / metabolism
  • Trypanosoma brucei rhodesiense / drug effects
  • Trypanosomiasis, African / drug therapy
  • Trypanosomiasis, African / mortality

Substances

  • Guanidines
  • Imidazolines
  • Nucleoside Transport Proteins
  • P2 transporter, Trypanosoma brucei
  • Trypanocidal Agents
  • DNA